The present invention relates to anhydrous, liquid antimicrobial suspension compositions of quaternaries prepared from hexamethylenetetramine and certain halohydrocarbons in admixture with an anhydrous carrier liquid and a thixotropic material. These compositions are chemically, physically and color stable when stored over extended time periods of at least six months.
Quaternaries prepared from hexamethylenetetramine and halohydrocarbons are old and well known antimicrobial agents as disclosed in Applied Microbiology, Volume 10, pages 211-216, 1962. For example, 1-(benzyl)-3,5,7-triaza-1-azoniaadamantane chloride is prepared from the reaction of hexamethylenetetramine with benzyl chloride; 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride and the cis- and cis-trans isomers thereof are prepared from the reaction of hexamethylenetetramine with 1,3-dichloropropene; 1-(xcex1-(2-xylyl))-3,5,7-triaza-1-azoniaadamantane chloride is prepared from the reaction of hexamethylenetetramine with xcex1-chloro-2-xylene and 1-(methylacetyl)-3,5,7-triaza-1-azoniaadamantane chloride prepared from the reaction of hexamethylenetetramine with methylchloroacetate.
The compound 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is commercially available from The Dow Chemical Company under the trademark DOWICIL(trademark) 200, hereinafter referred to as the xe2x80x9ccis-compound,xe2x80x9d and the various cis-/trans-mixtures of said compound containing from about 50 to 99.5 percent cis-isomer and about 50 to 0.5 percent trans-isomer are commercially available from The Dow Chemical Company under the trademarks DOWICIL(trademark) 100 and DOWICIL(trademark) 75.
The quarternary compounds are particularly effective antimicrobial agents and have been used in products such as, emulsified cutting oils, latexes, latex and emulsion paints, printing inks, glues and adhesives, coatings, sizings, hydraulic fluids and paper pulp dispersions.
Many antimicrobial agents used in cosmetic and personal care formulations, for example, are sold in the form of powder compositions. Formulators who use antimicrobial powder compositions in cosmetic and personal care formulations find themselves further faced with the many handling concerns associated with powders such as dust and mixing problems during product formulation. Many of the known quarternary compound powder compositions cannot conveniently be used in certain personal care products such as hand creams, lotions, shampoos and hand soaps because of mixing and stability problems.
It is therefore often desirable to employ the quarternary compound antimicrobial agents in the form of liquid concentrates since in many situations, liquids are more convenient to handle, and the inherent concerns associated with the use of powders, as mentioned hereinabove, are avoided. Such liquid compositions should be both chemically and physically stable over extended time periods of at least six months under a variety of storage conditions while maintaining their antimicrobial activity. Such compositions should also remain substantially color stable under said storage conditions.
Previous efforts to develop liquid concentrates of quarternary compounds which are homogeneous, color stable, and chemically and physically stable for extended periods of time have been generally unsuccessful. For example, 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride and its various cis- and trans-mixture are initially antimicrobially active in the presence of water and many other polar solvents, they do not however possess sufficient stability in such polar solutions to remain stable when held under conventional storage conditions for long periods of time.
The known liquid compositions of the cis- or cis/trans-isomers of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride have not been found acceptable for commercial use as many of the solvents or carrier liquids employed in these compositions do not provide sufficient stability for said compositions. For example, many organic solvents such as methanol, dimethylformamide, dimethylsulfoxide, monoethanolamine and, propylene glycol methyl ether, and the like, when in a solution, suspension or slurry with the cis-compound or the cis/trans-compounds over a short time form a marked darkening of the color of the composition. This characteristic is particularly unsuitable in the cosmetic industry, latex industry or any other such industry where color is an important parameter.
It is also well known that the quarternary compounds and specifically the cis- and the cis/trans-isomers of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride compounds when present in greater than 10 percent by weight in aqueous compositions will darken in color and lose much of their antimicrobial activity after a time period as short as one month. For example, a conventional 30 percent aqueous solution of either the cis- or the cis/trans-compound degrades in color in less than 24 hours after admixture and shows about a 30 percent chemical degradation within one month.
It would be therefore desirable to provide homogeneous, color stable, and chemically and physically stable liquid concentrate compositions containing quarternary compounds and specifically 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride and its cis- and cis/trans-isomers as active ingredients.
This invention relates to stable liquid suspension concentrate compositions comprising quaternaries from the group consisting of 1-(benzyl)-3,5,7-triaza-1-azoniaadamantane chloride, 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride and the cis- and cis/trans isomers thereof, 1-(xcex1-(2-xylyl))-3,5,7-triaza-1-azoniaadamantane chloride and methyl 1-(3,5,7-triaza-1-azoniaadamantane chloride)acetate in admixture with an anhydrous carrier liquid and a thixotropic material as an anti-settling agent.
This invention further relates to stable liquid suspension concentrate compositions comprising a 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride compound in either the cis or cis/trans-isomer form in admixture with an anhydrous carrier liquid and a thixotropic material as an anti-settling agent. The above compositions are substantially stable to color or chemical degradation and to changes in their physical makeup when they are stored under conventional storage conditions for time periods of up to six months or more.
The suspension compositions of the present invention containing the quaternaries in admixture with the anhydrous carrier liquid and the thixotropic material are liquids which remain substantially color stable for extended periods of at least six months under conventional storage, packaging, and handling conditions.
The liquid suspension concentrate compositions of the present invention are also chemically and physically stable and contain the quaternaries in an amount from about 0.9 to about 75 percent by weight, preferably from about 30 to about 50 percent by weight; the anhydrous carrier liquid is present in an amount from about 25 to about 99 percent by weight; and the thixotropic material is present in an amount from about 0.1 to about 10 percent by weight, preferably from about 0.2 to about 6.0 percent by weight, most preferably from about 0.3 to about 3.0 percent by weight.
As used herein, the term xe2x80x9canhydrousxe2x80x9d describes a material composition wherein the color thereof remains substantially the same for the above defined time period having a water content of less than 2.0 percent by weight.
As used herein, the term xe2x80x9ccolor stablexe2x80x9d describes a composition wherein the color thereof remains substantially the same for the above defined time period.
As used herein, the term xe2x80x9cchemically stablexe2x80x9d describes a composition wherein there is substantially no chemical degradation thereof and/or loss of antimicrobial activity for the above-defined time period.
As used herein, the term xe2x80x9cphysically stablexe2x80x9d describes a composition wherein there is substantially no particle separation or settling for the above-defined time period.
The suspension compositions of the present invention are easily handled, and can be employed directly as antimicrobial agents or diluted with conventional inert diluents or substrates, such as water or, alcohols, and the like to prepare ultimate treatment compositions for application to bacteria and fungi or to their habitat.
The quaternaries which are the active antimicrobial materials of the present compositions and which are prepared from the reaction of hexamethylenetetramine with 1,3-dichloropropene, benzyl chloride, 2-chloro-xcex1-xylene or methyl chloroacetate are antimicrobially active in the presence of water. These materials, however, have been found to possess insufficient storage stability when made into aqueous concentrate solutions to permit convenient long-term storage and shipping of the concentrates. For example, a concentrated aqueous solution containing more than about 2 percent of either the cis-compound and the cis/trans-compound lose a substantial amount of its biocidal activity under extended storage conditions.
The suspension compositions of the present invention show substantially no color or chemical degradation and demonstrate substantially no loss of antimicrobial activity with storage times of at least six months.
In preparing the suspension compositions of the present invention, the specific order of adding the various ingredients is not critical. In one method, the quaternary compound is mixed in the anhydrous carrier liquid and the thixotrope is added thereto to form a suspension. It is preferred, however, that the quaternary compound is added to a solution of the anhydrous carrier liquid and the thixotrope. Mixing is carried out at ambient temperatures under conditions of high sheer and results in physically stable homogeneous suspensions.
The quaternaries employed in the practice of the present invention are prepared by the reaction of hexamethylenetetramine with either 1,3-dichloropropene, benzyl chloride, 2-chloro-xcex1-xylene or methyl chloroacetate in the presence of a nonaqueous solvent at room temperature. As indicated hereinabove, such preparative procedures are taught in Applied Microbiology, Volume 10, pages 211-216, 1962. A conventional method for the preparation of the various cis- and trans-mixtures is found in U.S. Pat. No. 3,228,829. Both of the above references are incorporated herein by reference.
The anhydrous carrier liquids useful in the practice of the present invention are those which do not cause a reduction of antimicrobial activity of the quaternary material and cause no substantial yellowing or color changes of the quaternary-containing composition, nor any chemical changes during storage under conventional conditions for time periods of up to six months or more.
To determine if a specific anhydrous carrier liquid is useful as a carrier liquid, a 30 weight percent solution of one of the quaternaries in the solvent is prepared and stored at room temperature for one month or if a more rapid determination is desired, the solution is held at a temperature of about 45xc2x0 C. for about one week. The above solutions are analyzed for chemical degradation by HPLC, as hereinafter described, and comparing the sample against a freshly prepared control sample and any chemical degradation should be less than 10 percent for the carrier liquid is to be acceptable. The color of the sample is rated according to the Gardner color scale, as hereinafter described, and if the Gardner color is 3 or less, the solvent can be used; and if it is above 3, the solvent is not acceptable.
Representative carrier liquids include anhydrous surfactants from the alkoxylated alcohols and fatty acids and oil groups such as AETHOXAl(trademark) B, which is PPG-5-Laureth-5, a proprietary product of Henkel Corporation, AEROSURF(trademark) 66E10, which is Isosteareth-10, a proprietary product of Witco Incorporated, CROVOL(trademark) A-40, which is PEG-20 corn glycerides, a proprietary product of Croda Incorporated, GRILLOCAM(trademark) 20, which is Methyl gluceth-20, a proprietary product of Rita Corporation, HEXOTOL(trademark) L-9, which is Laureth-9 and HEXOTOL(trademark) OA-3 Special, which is Oleth-3, these are proprietary products of Heterene Incorporated, IGEPAL(trademark) CO-630, a nonylphenoxypoly(ethyleneoxy)ethanol, which is a proprietary product of Rhone-Poulenc, NOPALCOL(trademark) 4-L, which is PEG 400 monolaurate, NOPALCOL(trademark) 12-R, which is PEG 1200 castor oil, a proprietary product of Henkel Corporation, PEGOSPERSE(trademark) 400DL, which is PEG 400 dilaurate, a proprietary product of Lonza Incorporated, TERGITOL(trademark) 15-S-3 and TERGITOL(trademark) 15-S-9, which are C11-C15 secondary alcohol ethoxylates and are proprietary products of Union Carbide Corporation; glycerides such as NEOBEE(trademark) M-5, which is caprylic/capric triglyceride, a proprietary product of Stepan Company; polyglycols such as POLYGLYCOL(trademark) BM45-1600, a polyglycol which is a proprietary product of The Dow Chemical Company; RITABATE(trademark) 20, which is polysorbate-20, a proprietary product of Rita Corporation; glycol ethers such as tripropylene glycol methyl ether; or natural fatty oils such as mineral oil, lanolin oil and safflower oil; and other materials such as propylene carbonate, toluene and acetone. The ultimate concentration of the anhydrous carrier liquid in the suspension concentrate is from about 25 weight percent to about 99 weight percent of the surfactant and preferably from about 50 to about 70 weight percent.
The thixotropic materials useful in the practice of the present invention are those which do not cause a reduction of antimicrobial activity of the quaternary material and cause no substantial settling of the quaternary containing concentrate composition during storage under conventional conditions for time periods of up to six months or more.
To determine if a specific thixotropic material is useful, a 30-40 weight percent solution of one of the quaternaries in one of the carrier liquids is prepared. To this solution is added about 1-5 weight percent of the thixotropic material to be tested. The viscosity of the solution is measured at agitator speeds of 10, 20 and 100 RPM. If the viscosity of the solution is increased over that of a control solution consisting only of the quaternary and the carrier liquid, the thixotropic material is acceptable.
Representative thixotropic materials useful in the practice of the present invention include surface treated fumed silicas such as AEROSIL(trademark) R202, which is polymethyl-siloxane hydrophobic fumed silica and AEROSIL(trademark) R805, which is trimethyloctylsilane hydrophobic fumed silica which are proprietary products of Degussa Corporation; organically modified smectite clays such as BENTONE(trademark) 27, a trialkylammonium hectorite, BENTONE(trademark) 34, a tetralkylammonium bentonite, BENTONE(trademark) 38, a tetralkylammonium hectorite, BENTONE(trademark) GEL MIO, a tetralkylammonium hectorite/mineral oil/propylene carbonate mixture and hydrostearate derivatives such as THIXCIN(trademark) R, which is glyceryl tris-12-hydroxystearate and THIXATROL(trademark) ST, a modified glyceryl tris-12-hydroxystearate which are proprietary products of Rheox Inc., CLAYTONE(trademark) APA, a stearalkonium bentonite and FLOWTONE(trademark) R, which is trihydroxysterin, which are proprietary products of Southern Clay Products, Incorporated; SYNCROWAX(trademark) HRSC, a glyceryl tribehenate and calcium behenrate mixture, which is a proprietary product of Croda, Incorporated; TROYTHIX(trademark) XYZ, a castor oil derivative, which is a proprietary product of Troy Corporation. The ultimate concentration of the thixotropic material in the suspension concentrate is from about 0.1 weight percent to about 10 weight percent of the thixotropic material and preferably from about 0.2 to about 6.0 weight percent.
The quaternary compound containing suspension compositions of the present invention can be mixed in a wide variety of products which are subject to microbial attack such as, for example, emulsified cutting oils, latexes, latex and emulsion paints, printing inks, glues and adhesives, coatings, sizings, hydraulic fluids, paper pulp dispersions and cosmetic and personal care formulations.
The suspension compositions are added in amounts sufficient to provide an antimicrobially effective amount of the quaternary compounds in the product.
When the suspension compositions of the present invention are used in personal care items such as shampoos, the suspension compositions can also act as foam boosters and viscosity enhancers. The suspension compositions can also be used in personal care products such as cosmetics including lotions or creams and the like where they can act as emulsifiers, solubilizers and conditioners.
As used herein, the term xe2x80x9cantimicrobially-effective amountxe2x80x9d refers to that amount of the active quaternary compounds needed to exhibit inhibition of selected microorganisms. Ultimate concentrations of the active compounds in the products to which they are added is from about 0.02 weight percent to about 0.3 weight percent of the active compound and preferably from about 0.1 to about 0.2 weight percent and such amounts are generally suitable for antimicrobial use in most applications. The exact concentration of the compounds to be added to the product may vary within a product type depending upon the specific components of the product and the final uses of the product.
As used herein, the term xe2x80x9cmicroorganismxe2x80x9d is meant to refer to bacteria, fungi, viruses, algae, subviral agents and protozoa.
The terms xe2x80x9cinhibitionxe2x80x9d, xe2x80x9cinhibitxe2x80x9d or xe2x80x9cinhibitingxe2x80x9d as used in the present invention refer to the suppression, stasis, kill, or any other interference with the normal life processes of microorganisms that is adverse to such microorganisms, so as to destroy or irreversibly inactivate existing microorganisms and/or prevent or control their future growth and reproduction.